As people around the world regard 2020 as the year of COVID-19, the medical community considers this year to be the second-best year, shared with the year 1996, with respect to the number of drug molecules approved by the US Food and Drug Administration (FDA). Both years, 2020 and 1996, had a record of 53 new drug molecules approved by the FDA. In the year 2020, 53 new chemical entities and 13 biological medicines were approved, including 10 monoclonal antibodies, 2 antibody-drug conjugates, 3 peptides, and 2 oligonucleotides. Among them, most of the compounds were found to have fluorine or fluorine-containing functional groups exhibiting numerous pharmacological activities. Herein, we summarized the trifluoromethyl (TFM, -CF3)-group-containing FDA-approved drugs for the last 20 years. This article specially features and details the previous 20-year literature data, covering CF3-incorporated potential drug molecules, including their syntheses and uses for various diseases and disorders. The review covers the detailed chemistry of 19 FDA-approved drugs in the past 20 years, which contains the TFM group as one of the pharmacophores.

It is a very alarming situation for the globe because 55 million humans are estimated to be affected by Alzheimer’s disease (AD) worldwide, and still it is increasing at the rapid speed of 10 million cases per year worldwide. This is an urgent reminder for better research and treatment due to the unavailability of a permanent medication for neurodegenerative disorders like AD. The lack of drugs for neurodegenerative disorder treatment is due to the complexity of the structure of the brain, mainly due to blood–brain barrier, because blood–brain drug molecules must enter the brain compartment. There are several novel and conventional formulation approaches that can be employed for the transportation of drug molecules to the target site in the brain, such as oral, intravenous, gene delivery, surgically implanted intraventricular catheter, nasal and liposomal hydrogels, and repurposing old drugs. A drug’s lipophilicity influences metabolic activity in addition to membrane permeability because lipophilic substances have a higher affinity for metabolic enzymes. As a result, the higher a drug’s lipophilicity is, the higher its permeability and metabolic clearance. AD is currently incurable, and the medicines available merely cure the symptoms or slow the illness’s progression. In the next 20 years, the World Health Organization (WHO) predicts that neurodegenerative illnesses affecting motor function will become the second-leading cause of mortality. The current article provides a brief overview of recent advances in brain drug delivery for AD therapy.